This is a K24 proposal to continue mentoring in patient-oriented research related to substance use and associated syndemic problems in HIV prevention and care. I propose to continue my mentoring with a shift in primary focus from mental health to the role of substance use and related syndemics on biological HIV prevention approaches. New biological HIV prevention techniques, including early antiretroviral therapy (ART), are dependent on adequate adherence, and substance abuse and associated syndemics are known barriers. Candidate. I have 15 years of NIH-funded support addressing co-occurring psychosocial problems such as substance use in the context of interventions for HIV/AIDS. This includes interventions for adherence in HIV treatment, and domestic and international primary and secondary prevention studies (independently, through NIAID trial networks, and through mentee projects). I also have a strong and consistent successful mentoring history, including over 50 fellows and junior faculty, resulting in >150 publications wit mentees as first author (?70 mentee first author publications during the first 3.5 years of suppor for my current K24). Mentoring Plan. I have a large and steady set of requests to mentor junior level clinical researchers across disciplines with an interest in substance use / syndemics in the context of HIV prevention and care. I have access to psychology / behavioral medicine mentees from local clinical psychology and psychiatry training programs, access to local physician and public health mentees through the Harvard University CFAR, which encompasses all of the Harvard institutions. I am also receiving increasing numbers of requests to mentor national and international colleagues in behavioral science / substance use through sources such as the CFAR and NIAID CTU networks (e.g., HPTN diversity scholars). These mentees typically require mentoring in behavioral intervention development, testing, and dissemination, including incorporating behavioral science into biomedical or epidemiological research projects. The current proposal would allow me to continue to accommodate these requests through protected time for mentoring, and focus on requests in areas consistent with the substance- use theme of this proposal. Research Plan. In addition to my existing projects, I will leverage current and past funded projects to provide an additional platform for mentee involvement in this patient oriented substance use related research. One international and one domestic project are proposed, with each having a quantitative and a qualitative component. First, using data from a recently completed study-HPTN063, a one year observational study of sexually active HIV-infected patients in care in Brazil, Thailand, and Zambia (I am protocol chair)-we will examine the impact of substance use and associated syndemics on ART adherence and condomless sex acts across risk group and geographical settings. Second, using CNICS as a platform (I am an active collaborator), we will examine the impact of substance use and associated syndemics on the estimated number of HIV transmissions occurring by risk group (e.g., MSM, heterosexual women and men).